The present invention relates to wettable powder compositions of an ionophore antibiotic useful as a feed supplement to a ruminant animal (including a suckling ruminant juvenile animal), methods of using such a composition in conjunction with milk and/or milk replacement powders and as a milk replacer for such ruminant animals and related means and methods.
In U.S. Pat. No. 3,839,557 of Eli Lilly and Company (the fill content of which is hereby here incorporated by reference) there is disclosure of a method of increasing the efficiency of feed utilisation by ruminant animals having a developed rumen function where an antibiotic chosen from the group A204 (U.S. Pat. No. 3,705,238) dianemycin (fermentation product of Streptomyces Hygroscopicus NRRL 3444) monensin (U.S. Pat. No. 501,358), X537A (Netherlands patent 70.12,108) nigericin (U.S. Pat. No. 3,555,150) and X206 (1951, Berger et al, J. Am Chem. Soc. 73, 5295-98 (1951)), and certain derivatives thereof are orally administered to the ruminant animals whose fed efficiency is to be increased.
Examples of appropriate ruminant animals given are cattle, sheep and goats.
The invention of U.S. Pat. No. 3,839,557 is indicated as being useful to ruminants which have a developed rumen function. Young ruminants (basically those still unweaned) are stated as functioning as monogastic animals and that it is not until such young ruminant eat solid feed contain cellulose, starch and other carbohydrates that the function of the rumen begins to develop and the microbiological population of the rumen increases.
Dosages given in U.S. Pat. No. 3,839,557 (in general propionate-increasing amounts) are in the range of from about 0.05 mg of antibiotic per kg of body weight per day to about 2.5 mg/kg/day.
Administration methods given in U.S. Pat. No. 3,839,557 suggest incorporation of the antibiotic compound or compounds into tablets, drenches, boluses or capsules. Them is disclosure that drenches of such antibiotics can be prepared most easily by choosing a water soluble form of the antibiotic but that if an insoluble form is desired for some reason a suspension can be made. There is an indication that suspensions of insoluble forms of the antibiotics can be prepared in non solvents such as water but that suitable physiologically-acceptable adjuvants are necessary in order to keep the antibiotics suspended The adjuvants can be chosen from amongst thickeners, surfactants, hydrophilicity agents, density affecting agents and surface tension affecting agents.
U.S. Pat. No. 3,839,557 suggests that a suspendible antibiotic may be offered as a dry mixture of the antibiotic in adjuvants to be diluted before use. A suggestion is made that such antibiotic can be incorporated into drinking water by adding a water soluble or water suspendible form of the desired antibiotic to the water in a proper amount. There is also disclosure that the method of administration of the antibiotic can be practised in combination with other treatments, i.e. with other drugs used in combination.
European Patent Application 0139595 of Koffolk (1943) Limited relates to liquid feeds and milk replacers for ruminants and particularly for suckling ruminants. Such compositions that are disclosed contain ionophore antibiotics such as monensin, narasin, lasalocid (U.S. Pat. No. 3,715,372) and solinomycin.
In one form of the invention of EP 0139595 there is disclosed a liquid ionophore antibiotic composition for ruminants comprising an ionophore antibiotic and at least one non toxic water miscible organic solvent. The invention is also stated as providing a dry water soluble ionophore antibiotic composition suitable for combination with an aqueous medium to form a liquid composition for ruminants, the composition comprising an ionophore antibiotic, a non toxic water miscible organic solvent and a dry water soluble carrier therefor. The invention relates also to process for preparing liquid feeds which involves dissolving such an ionophore antibiotic in a non toxic water soluble organic solvent and admixing the resulting solution with a liquid feed, a water soluble vitamin concentrate or with drinking water.
The preferred ionophore antibiotics are those that have been subjected to an extraction process whereby the antibiotic is no longer in the mycelial form, i.e. is in a crystallisable form or a crystalline form.
Such compositions of EP 0139595 are stated as being liquid milk replacers, or at least being capable of being incorporated in liquid feeds or drinking water for administration to a suckling ruminant.
Example 13 of EP 0139595 refers to spraying in a horizontal mixer of a monensin solution (of the invention of EP 0139595 as defined) on a dry milk replacer and then the subsequent xe2x80x9cdissolvingxe2x80x9d thereof with water.
The present invention relates to an alternative milk replacer or milk extender composition to any of those disclosed and to related methods.
In a first aspect the present invention consists in a dry composition of an ionophore antibiotic capable of being suspended in water directly to form a suspension (with or without any other addition(s)) deliverable into a ruminant (particularly a suckling ruminant) or, capable upon admixture with a dry milk powder and/or milk substitute powder, of in turn then being mixed with water to form (with or without any other addition(s)) a suspension deliverable into a ruminant (particularly a suckling ruminant) as a milk replacement or extender, said composition comprising, when expressed weight for weight with respect to the overall dry composition,
from 10 to 95% (when expressed as the sodium salt) of at least one crystalline ionophore antibiotic,
from 0 to 10% antifoam agent(s),
from 0.1 to 20% wetting and/or surfactant agent(s),
from 0.1 to 10% dispersal agent(s), and
from 0.1 to 20% suspension agent(s).
As used herein percentages of ionophore antibiotic refer to the antibiotic in any suitable form (eg. acid or salt) but expressed for the purpose of the ranges by reference to its weight as the sodium salt as against the overall weight to the dry composition (where for the purpose of the overall weight the antibiotic is also accounted for by reference to its weight as the sodium salt).
Preferably said antibiotic is from 90 to 95% w/w
Preferably said antifoam agents is from 0 to 2% w/w
Preferably said wetting surfactant agents is from 0.1 to 5% w/w.
Preferably said dispersal agent is from 0.1 to 5% w/w
Preferably said suspension agent is from 0.1 to 5% w/w.
A preferred composition has
from 10 to 95% (eg. 10 to 80%) of at least one crystalline ionophore antibiotic,
from 0.1 to 0.5% antifoam agent(s),
from 0.1 to 0.5% wetting and/or surfactant agent(s),
from 0.1 to 0.5% dispersal agent(s), and
from 0.1 to 0.5% suspension agent
Preferably said ionophore antibiotic is selected from group consisting of Monensin, Lonomycin, Ionomycin, Laidlomycin, Nigericin, Grisorixin, Dianemycin, Lenoremycin, Salinomycin, Narasin, Antibiotic X206, Alborixin, Septamycin, Antibiotic A204, Maduramicin and Semduramicin, Compound 47224, Lasalocid (also including factors A, B, C, D and E), Mutalomycin, Isolasalocid A, Lysocellin, Tetronasin, Echeromycin, Antibiotic X-14766A, Antibiotic A23187, Antibiotic A32887, Compound 51532 and K41.
Preferably said ionophore antibiotic is Monensin.
Preferably said Monensin is Sodium Monensin.
Preferably said antifoaming agent is selected from the group consisting of Silicone antifoam powder such as Wacker ASP 3 hereinafter referred to.
Preferably said wetting agent is selected from the group consisting of Sodium lauryl sulfate (anionic sulfates) such as CARSONOL(trademark) SLS-R (LONZA) or EMAL(trademark) (POLEKAO).
Preferably said dispersal agent is selected from the group consisting of colloidal anhydrous silica such as Aerosil 200 Chemische Fabrik Kirsh Gmbtt.
Preferably said suspension agent(s) is or are selected from the group consisting of refined food grade galactomannan such as guar gum.
In a further aspect the present invention consists in the use of a dry composition in accordance with the present invention after admixture with water to form a suspension as a feed supplement of a suckling or other ruminant.
Preferably said use involves milk powder or a milk substitute which is mixed into water either subsequently to, simultaneously with or prior to the suspension of the composition of the present invention in such water.
The present invention also consists in, as a dry composition, a dry composition in accordance with the present invention and a milk powder and/or milk replacement powder.
In yet a further aspect the invention consists in a calf feed composition comprising a substantially homogeneous aqueous suspension of, with respect to the composition volume,
(i) from 2 to 16 mg/L of a dry composition in accordance with the present invention,
(ii) optionally, a milk replacer composition, and
(iii) optionally, a milk extender composition.
Preferably from 5 to 30 g/L of a dry milk replacer composition has been included.
Preferably 10 to 25 g/L, eg. 15, or 20 g/L.
Preferably from 1 to 3 g/L milk extender (preferably about 2 g/L) is present or, preferably, is present in addition to a or the dry milk replacer composition.
In yet a further aspect the invention consists in a dry composition of monensin capable of being suspended in water directly to form a suspension (with or without any other addition(s)) deliverable into a ruminant or, capable upon admixture with a dry milk powder and/or milk substitute powder, of in turn then being mixed with water to form (with or without any other addition(s)) a suspension deliverable into a ruminant as a milk replacement or extender, said composition comprising, when expressed weight for weight with respect to the overall dry composition,
95% (when expressed as the sodium salt), of crystalline sodium monensin,
19% silicone antifoam powder,
3.5% sodium lauryl sulfate,
2.5% colloidal anhydrous silica, and
1.5% Guar gum
In a still further aspect the invention consists in a calf feed composition comprising a substantially homogeneous aqueous suspension of, with respect to the composition volume,
(I) from 2 to 16 mg/L of a composition comprising
95% (when expressed as the sodium salt) of crystalline sodium monensin,
19% silicone antifoam powder,
3.5% sodium lauryl sulfate,
2.5% colloidal anhydrous silica, and
1.5% Guar gum, AND
(II) 15 to 20 g/L of a milk replacer composition, and/or 1 to 3 g/L of a milk extender composition.
In still a further aspect the invention consists in, as a premix. The components (i) and (ii), (i) and (iii) or (i), (ii) and (iii) for a calf feed composition as defined hereinbefore.
In still a further aspect the present invention consists in a method of increasing feed conversion and growth rate of suckling ruminants which involves the administration orally or self administration orally of a composition of the present invention in conjunction with at least water into such ruminants.
Coccidiosis is a serious and common disease of dairy calves. During much of the time that dairy calves are at risk of coccidiosis, some or all or their diet comprises milk, milk replacers or milk extenders. The intake of these milk components is more consistent and controllable than other components of the diet. For this reason it is desirable to be able to administer anti-coccidial agents to these animals in the milk portion of their diet.
Monensin sodium in prior art formulations does not remain evenly distributed in milk, milk replacers or milk extenders for a sufficient period time to make it practical or safe for use in this manner.
A xe2x80x9cmilk extenderxe2x80x9d contains vitamins and minerals but in itself is not a xe2x80x9cmilk replacerxe2x80x9d.
Milk replacers are, as the name suggests, compositions capable of replacing the natural milk of the species. Typically a milk replacer is made up from a skim milk powder (usually of the same species of mammal) plus a source of fat which can either be of animal or plant origin. In the case of cattle this fat replaces the normal cream in whole cows milk.
The present invention therefore envisages a calf feed to supplement or replace the natural milk feed of an animal. The calf feed may comprise
i) a milk replacer having an anti coccidial agent provided in accordance with the present invention, substantially evenly distributed there throughout
ii) a milk replacer and milk extender mixed/blended composition itself including an anti coccidial agent (whether blended with the milk replacer, the milk extender or both simultaneously).
Calves receive and ingest milk replacers and extenders within 24 hours of preparation.
Monensin was selected as the ionophore antibiotic for detailed trialing.
To ensure the safety of monensin wettable powder as a delivery vector for ingestion as a liquid it was considered necessary that monensin, delivered as part of a calf feed eg. An aqueous composite as a milk replacer and/or milk extender, should remain evenly distributed for 24 hours after homogeneous mixing with water.
The purpose of these trials was to determine the distribution characteristics of monensin wettable powder in aqueous preparations of milk replacers and milk extenders.
A preferred form of monensin wettable powder of the present invention having the formula as follows was used in the following trials and assays.
Monensin (Sodium) Wettable Powder
A preferred dry composition of an ionophore antibiotic (this includes a mixture of different types) comprises
10 to 95% of at least one crystalline ionophore antibiotic (the percentage being when the antibiotic is expressed as its sodium salt (eg. Monensin sodium whether or not it is in fact a monensin salt or indeed a sodium salt),
0 to 2% antifoam agent(s),
0.1 to 5% wetting and/or surfactant agent(s),
0.1 to 5% dispersal agent(s), and
0.1 to 5% suspension agent.